Age-dependent control of collagen-dependent platelet responses by thrombospondin-1—comparative analysis of platelets from neonates, children, adolescents, and adults

Katrin Herken, Martin Glauner, Stefanie C. Robert, Matthias Maas, Sonja Zippel, Ulrike Nowak-Göttl, Barbara Zieger, Judith Lahav, Anke C. Fender, Kerstin Jurk*, Beate E. Kehrel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Platelet function is developmentally regulated. Healthy neonates do not spontaneously bleed, but their platelets are hypo-reactive to several agonists. The mechanisms underlying immature platelet function in neonates are incompletely understood. This critical issue remains challenging for the establishment of age-specific reference ranges. In this study, we evaluated platelet reactivity of five pediatric age categories, ranging from healthy full-term neonates up to adolescents (11–18 years) in comparison to healthy adults (>18 years) by flow cytometry. We confirmed that platelet hypo-reactivity detected by fibrinogen binding, P-selectin, and CD63 surface expression was most pronounced in neonates compared to other pediatric age groups. However, maturation of platelet responsiveness varied with age, agonist, and activation marker. In contrast to TRAP and ADP, collagen-induced platelet activation was nearly absent in neonates. Granule secretion markedly remained impaired at least up to 10 years of age compared to adults. We show for the first time that neonatal platelets are deficient in thrombospondin-1, and exogenous platelet-derived thrombospondin-1 allows platelet responsiveness to collagen. Platelets from all pediatric age groups normally responded to the C-terminal thrombospondin-1 peptide RFYVVMWK. Thus, thrombospondin-1 deficiency of neonatal platelets might contribute to the relatively impaired response to collagen, and platelet-derived thrombospondin-1 may control distinct collagen-induced platelet responses.

Original languageEnglish
Article number4883
JournalInternational Journal of Molecular Sciences
Volume22
Issue number9
DOIs
StatePublished - 1 May 2021

Funding

FundersFunder number
Medical Faculty of the Westfälische Wilhelms-University
International Myeloma Foundation

    Keywords

    • Collagen
    • Flow cytometry
    • Neonates
    • Platelets
    • Reference ranges
    • Thrombospondin-1

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